>Mothers keep on giving

We have further proof of yet another naturally occuring adult stem cell line that contributes to treatment of diabetes in the recipient long after introduction of the cells and without immune rejection.

Scientists have reported in the “Proceedings of the National Academies of Science (Free abstract) about the discovery that mother’s stem cells may cross the placenta and that- in those babies who grow up and later develop Type I diabetes (“Juvenile Diabetes,” or “Insulin Dependent Diabetes Mellitis”) – some of those cells help repair the pancreas and make insulin.

The researchers thought they would find evidence that the maternal cells might actually cause the diabetes, but instead found that the maternal cells had become beta islet cells of the pancreas, the cells which produce insulin, and were functioning in a beneficial way, years later.

For the first time, scientists have discovered that cells passed from mother to child during pregnancy can differentiate into functioning islet beta cells that produce insulin in the child. The same study also found that maternal DNA was found in greater amounts in the blood of children and young adults with Type 1 diabetes than their healthy siblings and a control group, implying that they may be attempting to repair damaged tissue.The findings suggest a beneficial role for this type of maternal microchimerism. Microchimerism is the term used when an individual harbors cells or DNA that originate from another genetically distinct individual.

In this study, published in the Jan. 22 issue of the Proceedings of the National Academy of Sciences, J. Lee Nelson, M.D., a member of the Clinical Research Division at Fred Hutchinson Cancer Research Center, and colleagues found no evidence that the mother’s cells were attacking the child’s insulin cells and no evidence that the maternal cells were targets of an immune response from the child’s immune system.

“We think the maternal cells may be helping to regenerate damaged tissue in the pancreas,” Nelson said.

She said investigators are excited about new possible approaches to treat Type 1 diabetes raised by their findings. For example, if maternal microchimerism results in cells that make insulin, a mother’s stem cells might be harvested and used to treat her diabetic child. Such cells would have a genetic edge over donated islet cells from a cadaver that are usually completely genetically mismatched.

“The child is probably tolerant to the mother’s half-matched cells because the child acquired the cells during its life as a fetus while its immune system was still developing,” Nelson said.

Originally, the study of 172 individuals and pancreatic tissue from four males was designed to ask the question whether these small numbers of maternal cells might be involved in any way in Type 1 diabetes. “My initial theory was that perhaps, in some situations, too many mother cells cross over to the fetus at the wrong time, becoming beta cells that make insulin in the child. Could diabetes result because the child lost tolerance to those cells because they are genetically half foreign? Our research disproved this,” she said.

Instead, the researchers found a small number of female islet beta cells in male pancreatic tissue (procured from autopsies) that produced insulin. “To our knowledge a maternal contribution to endocrine function has not previously been described,” the authors said. “Our findings also raise the possibility that naturally acquired microchimerism might be exploited to therapeutic benefit.”

The study found significantly higher levels of maternal DNA in the peripheral blood of 94 children and adults with Type 1 diabetes as compared to 54 unaffected siblings and 24 unrelated healthy subjects they studied. Maternal microchimerism first was recognized in children with severe combined immunodeficiency in the 1970s. In 1999, a study by Nelson et al was first to show that maternal microchimerism persists into adulthood for persons with uncompromised immune systems (Journal of Clinical Investigation 104:41-47).

“If cells with the potential to produce insulin can pass from mother to child during pregnancy, without the child’s immune system destroying them as seems to be the case here, then this could open up promising new avenues of research, and perhaps provide a new source of insulin-producing cells for therapeutic use.”

Where did the stem cells come from in the mother? How are they preserved in the child through the years, even when mom and child would not be considered a good “tissue match” for organ donation? And how are they stimulated and recruited to the necessary tissues and organs in order to contribute to the repair and function of the child’s tissues? How can we mimic and maximize the process when and where we want?

All of these questions are fertile ground for research. And not a one of the answers will depend on the destruction of a human being.

There’s coverage in the January 22 Washington Post. However, the article states that Type I diabetes is inherited. The tendency may be inherited, but I don’t believe that anyone has determined the actual gene or any specific trigger that can be said to cause Type 1 diabetes, other than the patiint’s own immune system begins to make antibodies against the beta islet cells and insulin. Somehow, the mother’s cells aren’t affected in this case – which makes the discovery even more important and hopeful for patients: there has always been the concern that any new stem cells introduced into the patient would also be subjected to attack.